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Cryo-electron microscopy (cryo-EM) is a powerful technique in structural biology and drug discovery, enabling the study of biomolecules at high resolution. Significant advancements by structural biologists using cryo-EM have led to the…

Biomolecules · Quantitative Biology 2024-12-05 Yi Zhou , Yilai Li , Jing Yuan , Quanquan Gu

Cryo-electron microscopy (cryo-EM) has emerged as a powerful technique for determining the three-dimensional structures of biological molecules at near-atomic resolution. However, reconstructing helical assemblies presents unique challenges…

Quantitative Methods · Quantitative Biology 2026-03-16 Guy Shapira , Yoel Shkolnisky

Traditional sampling schemes often assume that the sampling locations are known. Motivated by the recent bioimaging technique known as cryogenic electron microscopy (cryoEM), we consider the problem of reconstructing an unknown 3D structure…

Signal Processing · Electrical Eng. & Systems 2024-04-16 Renke Wang , Francien G. Bossema , Thierry Blu , Pier Luigi Dragotti

Cryo-electron microscopy (cryo-EM) studies using single particle reconstruction are extensively used to reveal structural information on macromolecular complexes. Aiming at the highest achievable resolution, state of the art electron…

Cryo-electron microscopy provides 2-D projection images of the 3-D electron scattering intensity of many instances of the particle under study (e.g., a virus). Both symmetry (rotational point groups) and heterogeneity are important aspects…

Applications · Statistics 2019-05-17 Nan Xu , Peter C Doerschuk

Single-particle cryo-electron microscopy (cryo-EM) has become a cornerstone of structural biology, enabling near-atomic resolution analysis of macromolecules through advanced computational methods. However, the development of cryo-EM…

Computer Vision and Pattern Recognition · Computer Science 2025-10-07 Runmin Jiang , Genpei Zhang , Yuntian Yang , Siqi Wu , Minhao Wu , Wanyue Feng , Yizhou Zhao , Xi Xiao , Xiao Wang , Tianyang Wang , Xingjian Li , Muyuan Chen , Min Xu

Accurate orientation estimation is a crucial component of 3D molecular structure reconstruction, both in single-particle cryo-electron microscopy (cryo-EM) and in the increasingly popular field of cryo-electron tomography (cryo-ET). The…

Applications · Statistics 2026-02-25 Sheng Xu , Amnon Balanov , Amit Singer , Tamir Bendory

Single-particle cryo-EM has transformed structural biology but still faces challenges in resolving conformational heterogeneity at atomic resolution. Existing cryo-EM heterogeneity analysis methods either lack atomic details or tend to…

Biomolecules · Quantitative Biology 2025-10-21 Chengwei Zhang , Shimian Li , Yihao Niu , Zhen Zhu , Sihao Yuan , Sirui Liu , Yi Qin Gao

Cryo-electron tomography (cryo-ET) enables in situ visualization of macromolecular structures, where subtomogram analysis tasks such as classification, alignment, and averaging are critical for structural determination. However, effective…

Computer Vision and Pattern Recognition · Computer Science 2025-10-07 Runmin Jiang , Wanyue Feng , Yuntian Yang , Shriya Pingulkar , Hong Wang , Xi Xiao , Xiaoyu Cao , Genpei Zhang , Xiao Wang , Xiaolong Wu , Tianyang Wang , Yang Liu , Xingjian Li , Min Xu

Background and Objective: The contrast of cryo-EM images varies from one to another, primarily due to the uneven thickness of the ice layer. This contrast variation can affect the quality of 2-D class averaging, 3-D ab-initio modeling, and…

Computer Vision and Pattern Recognition · Computer Science 2022-07-01 Yunpeng Shi , Amit Singer

Cryogenic electron tomography is a technique for imaging biological samples in 3D. A microscope collects a series of 2D projections of the sample, and the goal is to reconstruct the 3D density of the sample called the tomogram.…

Computer Vision and Pattern Recognition · Computer Science 2024-08-13 Simon Wiedemann , Reinhard Heckel

Cryogenic Electron Tomography (CryoET) is a useful imaging technology in structural biology that is hindered by its need for manual annotations, especially in particle picking. Recent works have endeavored to remedy this issue with few-shot…

Quantitative Methods · Quantitative Biology 2024-07-10 Yizhou Zhao , Hengwei Bian , Michael Mu , Mostofa R. Uddin , Zhenyang Li , Xiang Li , Tianyang Wang , Min Xu

Structural flexibility and/or dynamic interactions with other molecules is a critical aspect of protein function. CryoEM provides direct visualization of individual macromolecules sampling different conformational and compositional states.…

Biomolecules · Quantitative Biology 2021-08-04 Muyuan Chen , Steven Ludtke

Cellular processes are governed by macromolecular complexes inside the cell. Study of the native structures of macromolecular complexes has been extremely difficult due to lack of data. With recent breakthroughs in Cellular electron cryo…

Quantitative Methods · Quantitative Biology 2018-06-12 Chengqian Che , Ruogu Lin , Xiangrui Zeng , Karim Elmaaroufi , John Galeotti , Min Xu

Motivation: Structural heterogeneity in single-particle cryo-electron microscopy (cryo-EM) data represents a major challenge for high-resolution structure determination. Unsupervised classification may serve as the first step in the…

Data Analysis, Statistics and Probability · Physics 2017-11-01 Jiayi Wu , Yong-Bei Ma , Charles Congdon , Bevin Brett , Shuobing Chen , Qi Ouyang , Youdong Mao

Cryo-electron microscopy is a revolutionary technique that can provide 3D density maps at near-atomic resolution. However, map validation is still an open issue in the field. Despite several efforts from the community, it is possible to…

Biological Physics · Physics 2019-08-06 Sebastian Ortiz , Luka Stanisic , Boris A Rodriguez , Markus Rampp , Gerhard Hummer , Pilar Cossio

Deep learning has demonstrated superb efficacy in processing imaging data, yet its suitability in solving challenging inverse problems in scientific imaging has not been fully explored. Of immense interest is the determination of local…

Materials Science · Physics 2019-02-20 Nouamane Laanait , Qian He , Albina Y. Borisevich

Protein structure prediction models are now capable of generating accurate 3D structural hypotheses from sequence alone. However, they routinely fail to capture the conformational diversity of dynamic biomolecular complexes, often requiring…

Machine Learning · Computer Science 2025-12-02 Rishwanth Raghu , Axel Levy , Gordon Wetzstein , Ellen D. Zhong

Cryo-Electron Microscopy (cryo-EM) has become an extremely powerful method for resolving structural details of large biomolecular complexes. However, challenging problems in single-particle methods remain open because of (1) the low…

Biomolecules · Quantitative Biology 2019-08-12 Shengnan Lyu , Christian Wülker , Yuqing Pan , Amitesh S. Jayaraman , Jianhao Zheng , Yilin Cai , Gregory S. Chirikjian

Single-particle electron microscopy is a modern technique that biophysicists employ to learn the structure of proteins. It yields data that consist of noisy random projections of the protein structure in random directions, with the added…

Applications · Statistics 2012-03-01 Victor M. Panaretos , Kjell Konis